Autophagy activated by the c‑Jun N‑terminal kinase‑mediated pathway protects human prostate cancer PC3 cells from celecoxib‑induced apoptosis

Zhu,Xin; Zhou,Mi; Liu,Guanyu; Huang,Xiaolong; He,Weiyang; Gou,Xin; Jiang,Tao

doi:10.3892/etm.2017.4287

Autophagy activated by the c‑Jun N‑terminal kinase‑mediated pathway protects human prostate cancer PC3 cells from celecoxib‑induced apoptosis

Authors:
- Xin Zhu
- Mi Zhou
- Guanyu Liu
- Xiaolong Huang
- Weiyang He
- Xin Gou
- Tao Jiang
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Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: March 30, 2017 https://doi.org/10.3892/etm.2017.4287
Pages: 2348-2354
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the role of autophagy in celecoxib-induced apoptosis in human hormone‑insensitive prostate cancer cell line PC3 cells and to explore the underlying molecular mechanism leading to autophagic activation. A cell viability assay was applied to investigate the effect of various concentrations of celecoxib (0, 40, 60, 80, 100 and 120 µmol/l) on PC3 cells for 24 and 48 h, respectively. The 50% inhibitory concentration of celecoxib for 24 h was chosen for subsequent experiments. Annexin V‑fluorescein isothiocyanate/propidium iodide double staining flow cytometry, as well as caspase 3 and poly (ADP‑ribose) polymerase proteins detected by western blotting, were applied to analyze cellular apoptosis induced by celecoxib. Ultrastructural cellular changes observed by transmission electron microscopy and the level of LC‑3 II and P62 detected by western blotting were used to determine the activation of autophagy. It was demonstrated that celecoxib induced apoptosis and activated autophagy in PC3 cells in a dose‑ and time‑dependent manner. Furthermore, flow cytometry and western blotting were applied to elucidate whether the role of autophagy in celecoxib‑induced apoptosis is protective or destructive. Blockade of autophagy markedly increased apoptosis, suggesting that celecoxib‑activated autophagy was cytoprotective. Additionally, c‑jun‑N‑terminal kinase (JNK) was demonstrated to have a role in autophagic activation, and suppression of JNK was able to reduce autophagy and increase apoptosis. In conclusion, the results of the present study indicate that celecoxib induces apoptosis in PC3 cells; however, celecoxib also activates JNK‑mediated autophagy, which exerts cytoprotective effects in prostate cancer PC3 cells. Blockade of autophagy via the JNK‑mediated pathway may provide a promising strategy for prostate cancer therapy.

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